Human immunodeficiency virus infection [HIV]

HIV is considered as a major global public health issue. According to the World Health Organization (WHO) globally in 2015, these facts are stated:

  • The total number of people infected with HIV ranges from 34.0 to 39.8 million.
  • New cases of individuals infected with HIV ranges from 1.8 to 2.4 million.
  • From 940 000 to 1.3 million people have died because of HIV-related causes.
  • Two-thirds of the total of new HIV infections are recorded in the sub-Saharan Africa. It is considered as the most affected region, with 23.1 to 28.5 million people who have been infected with HIV.

 

It is estimated that only 60% of people with HIV know their status for the time being. The remaining 40% or over 14 million people still are in need to access HIV testing services to check their current status.

Globally, in the 2016, 16.1 to 19.0 million patients infected with HIV were receiving antiretroviral therapy (ART).

National HIV programs supported by the civil society and a range of development partners were successful between the years 2000 and 2015 in:

  • Decreasing the number of new HIV infections by 35%.
  • Decreasing the number AIDS-related deaths by 28%.

 

By the year 2030, 21 million can survive death and 28 million new cases can be prevented by providing ART to all patients infected with HIV and expanding prevention choices.

Overview

Human immunodeficiency virus (HIV) causes an HIV infection. As progression is the nature of HIV, it develops to become acquired immunodeficiency syndrome (AIDS). HIV consists of two subtypes including, HIV-1 and HIV-2, where the main difference between these two types is the rate of progression to AIDS. HIV affects a certain type of white blood cells cluster of differentiation 4, abbreviated as (CD4) by gradually destroying these cells and using them to replicate. The more CD4 cells are destroyed, the weaker and more compromised the immune system becomes. There are three phases for an HIV infection, acute HIV infection phase where the virus replicates rapidly and the CD4 count decreases, clinical latency phase by which the virus is still active but with a low level of replication rate, and is usually symptomless in patients, and the last phase is AIDS which is the advanced phase of the disease.    

Infection with HIV occurs by body fluids such as blood, semen, vaginal fluid, and from pregnant women to the fetus. Unsafe exposure to these fluids like having unprotected sex or sharing needles with others puts the person in a risk of getting infected with HIV. Avoiding risk factors is helpful in preventing the infection from occurring.   

The symptoms of HIV infection vary according to the phase of the virus. In an acute HIV infection phase, patients develop flu-like symptoms. In clinical latent phase, there are no specific symptoms except for the swelling of the lymph nodes that might occur. When the disease progresses to AIDS, several symptoms will appear such as weight loss, fever, swelling of lymph nodes, in addition to other symptoms.  

The weakened immune system by HIV could lead to several complications such as opportunistic infections, cancers, neurological complications, wasting syndrome, and kidney disease.

The diagnosis of HIV depends on the presence of HIV antibodies in body fluids. No drug can cure HIV completely, but a combination of antiretroviral therapy (ART) are used to control the virus, manage the symptoms, and decrease the progression rate. When no treatment is used, the disease will progress to AIDS within ten years or less.

HIV is a major global public health issue. According to the World Health Organization (WHO)a total number of people infected with HIV are between 34.0 to 39.8 million, the number of new cases infected with HIV are 1.8 - 2.4 million, and around940 000 to 1.3 million people have died from HIV-related causes in 2015. 

Definition

Human immunodeficiency virus (HIV) causes an HIV infection. Acquired immunodeficiency syndrome, abbreviated as (AIDS) is considered the most advanced stage of an HIV infection. The targeted cells by HIV are the infection-fighting CD4 cells that belong to the immune system where it attacks and gradually destroys these cells, which increases the difficulty in the ability of the body to fight infections and certain cancers.

Subtypes

Two types of HIV can be differentiated genetically and antigenically:

  1. HIV-1

 It is the cause of the current pandemic HIV infection worldwide. This type of infection occurs when SIVcpz; a molecular chimera of SIVs from two or more different monkey species that originally infects chimpanzees infects humans in this case. 

There are three sub-groups of HIV-1 include:

  • M HIV-1.
  • N HIV-1.
  • O HIV-1.

 

  1. HIV-2

When simian immunodeficiency virus from sooty mangabey monkeys, abbreviated as (SIVsmm); a lentivirus closely related to SIV from macaques and the human immunodeficiency virus type 2 (HIV-2), and harbored by sooty mangabeys; natural hosts for SIV infection.

 It is widespread in West Africa, and rarely found in other places. The progress of AIDS in this type is slower than other types.

Causes

Mainly, body fluids spread HIV; a viral infection. These fluids include:

  • Sexual contact

 Having vaginal, anal or oral sex with a partner infected with HIV which allows the blood, semen or vaginal secretions to enter the other partner’s body. Some oral ulcers or small tears can occur during sexual activity, forming a passage for the virus to enter the body.

 

  • Blood transfusions

This happens when an individual receives blood contaminated with HIV. Nowadays, the majority of hospitals and blood banks screen the blood for HIV antibodies make the risk minimal.  

 

  • Sharing needles contaminated with HIV

 The infected blood that could contaminate needles and syringes can transmit the infection.

 

  • During pregnancy or delivery or through breastfeeding

The mother has to be infected with HIV in order to infect her baby. This happens via shared blood circulation and via breastfeeding milk. The risk of infection transmission to the fetus can be reduced by getting the appropriate treatment during pregnancy.

Risk Factors

HIV can occur with anyone. However, certain behaviors and conditions increase the risk for an individual to develop HIV such as:

  • Having unprotected anal or vaginal sex or frequent use of the same latex or polyurethane condom.
  • Having another sexually transmitted infection such as syphilis, herpes, chlamydia, gonorrhea, and bacterial vaginitis. The risk is increased by these infections via the open sores on the genitals they create which form a doorway for HIV to enter the body.
  • When intravenous drugs or shared needles and syringes are used, this could expose the people involved to droplets of other people's blood.
  • Men who do not undergo circumcision fall at higher risk of getting heterosexual transmission of HIV.
  • Receiving unsafe injections, blood transfusions, tissue transplantation.
Pathophysiology

CD4 is a specific type of white blood cell that helps the body fight diseases. When the body gets infected with HIV, the virus starts to break the CD4, leading to the deterioration of the immune system by the continuous destruction of more CD4 cells. When one of the cases of an AIDS-defining complication start or the CD4 count reaches a count under 200 cells/mm3, the patient infected with HIV progresses to AIDS which can take years to occur.

Clinical HIV infection undergoes three distinct phases as follows:

  1. Acute HIV Infection phase

An inverse relation correlates the number of CD4 cells with the number of the virus produced, where the more the virus is produced the less the CD4 cells are there since the virus uses the CD4 cells to replicate, leading to a rapid decrease in their number, in addition to their destruction.   . Following that, a viral set point is reached which means that numbers of the virus reach a decreased level and hence the level of the CD4 cells are increased but it may not return to pre-infection levels. Finally, the immune response will begin to bring the level of virus in the body back down to a level called a, which is a relatively stable level of virus in the body. The CD4 count starts to increase at this point, Start taking ART during this stage. Taking antiretroviral therapy (ART); is the use of HIV medicines to treat HIV infection, may be helpful in maintaining the patient’s health

 

  1. Clinical latency phase

This stage involves the virus being alive or developing but is symptomless, and therefore it could be called chronic HIV infection or asymptomatic HIV infection when the symptoms of the clinical latency stage do not show or only mild ones are present on the patient with HIV. The HIV virus is considered active during this stage and is with a low duplicating rate. Taking ART helps keep the virus suppressed which gives a life expectancy or clinical latency of several decades for When ART is not taken, the clinical latency stage lasts within 10 years with the exception of some patients who may have a rapid progress through this stage

 

  • 3. AIDS progression phase

 This stage of HIV infection occurs when the number of the CD4 cells decreases under 200 cells per cubic millimeter of blood (200 cells/mm3), and a serious damage to the immune system occurs. The body becomes more comprised to opportunistic infections, and the patient progresses to AIDS. A patient is diagnosed with progressed AIDS when one or more opportunistic illnesses are there despite what the count of CD4 cells count might be. Once the patient have progressed to AIDS, life expectancy is three years without treatment, unless the patient undergoes a dangerous opportunistic illness which lowers the life expectancy to 1 year.

Signs And Symptoms

The stage of infection defines the symptoms of HIV.

  • Acute HIV infection

Post infection; the first few weeks, individuals develop flu-like symptoms such as:

  • Fever.
  • Chills.
  • Headache.
  • Muscles ache and joints pain.
  • Skin rash.
  • Sore throat.
  • Swollen lymph glands, mainly in the neck.
  • Night sweats.
  • Fatigue.
  • Mouth ulcers.

 

This stage involves a high count of the virus in the bloodstream but with mild symptoms. The spread of acute infection phase HIV infection is wider than the following stage of infection. Some cases that are infected with HIV could be symptomless for 10 years or more.

 

  • Clinical latent infection (Chronic HIV)
  • This phase includes an active virus with slow growth rate, in addition to continuous damage to the white blood cells. Some cases include the swelling of lymph nodes that occurs during clinical latent HIV. Otherwise, there are no specific signs and symptoms. Taking ART the correct way as a treatment  for HIV can delay the occurrence of this phase into several decades. Without treatment, this stage may last a decade or longer   with the exception of some who might rapidly progress in this phase.

Although infected individuals may show no symptoms but are still able to transmit HIV to others during this phase. Viral suppression; having a very low level of virus in their blood and using ART (renders the transition of the virus to be become less likely than those who are not virally suppressed.

 

  • Progression to AIDS

It takes about 10 years for a person to have a weak immune system and the disease progress to AIDS, without treatment. AIDS is the late stage of an HIV infection where the immune system has been severely damaged, making the patient susceptible to opportunistic infections (diseases that usually don not cause problems in a person with a healthy immune system).

Symptoms can include:

  • Rapid weight loss.
  • Recurring fever.
  • Profuse night sweats.
  • Extreme and unexplained tiredness.
  • Prolonged swelling of the lymph glands in the armpits, groin, or neck.
  • Diarrhea that lasts for more than a week.
  • Sores of the mouth, anus, or genitals.
  • Pneumonia.
  • Red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose, or eyelids.
  • Memory loss, depression, and other neurologic disorders.
Diagnosis

HIV diagnosis is based on the presence of HIV antibodies in the body fluid which include blood, oral fluid, or urine. There are three types of tests available:

  • Antibody tests

Most rapid tests and home tests are included in this type .When the body is infected, the immune system starts to produce antibodies that can be detected via this test in the body fluid. A blood sample is easier for detection earlier after an infection than oral fluid that has a lower count of antibodies.

21-84 days are required to have what is called an HIV window period which is the time needed for a body to make enough antibodies so that an antibody test is able to detect the infection. The majority of patients will have detectable antibodies during this window period. When a negative result is shown during this window period, the test should be repeated three months after the possibility of getting infected with HIV.

  • The time needed for a rapid antibody screening test results to be ready is 30 minutes or less.
  • The OraQuick HIV Test uses an oral swab to provide fast results within 20 minutes. A kit is used to test an oral fluid sample where they are provided for purchase in stores or online. These tests can be used at home, or in some community and clinical testing programs.
  • The Home Access HIV-1 Test System is a home collection kit that collects a blood sample via pricking the finger and then sending it by mail to a licensed laboratory. Later on the result is delivered with confidentiality to the person involved, in addition to providing confidential counseling and referral to treatment.

A positive test result for any type of antibody obligates the person involved to take a follow-up test to confirm the result.  A first positive rapid home test requires a health care provider to get follow-up testing whereas a laboratory first positive rapid test requires follow-up testing by the laboratory which is done usually on the same blood sample as the first test.6

 

  • Combination or fourth-generation tests

 HIV antibodies and antigens are detected through these tests where the antigen is a component of the virus itself that is present during acute HIV infection and is considered as a foreign substance so the immune system, triggering it to become active in order to fight these antigens. In case of an infection with HIV, an antigen called p24 is produced even before antibodies develop.

HIV window period in this case needs13 to 42 days. If the test show negative result during the window period, the patient should repeat the test three months after the possibility of getting infected r with HIV. Nowadays a rapid combination tests is available.

 

 

  • Nucleic acid tests (NAT)

 This case detects HIV in the blood not the presence of antibodies which usually requires 7 to 27 days. The result comes out as a positive/negative result or the actual amount of virus present in the blood.

The accuracy of nucleic acid tests is considered high during the early stages of infection. However, some limitations are presented include:

  • It is a very expensive tests that is used in very narrow ranges, such as people who recently had a high-risk exposure or a possible exposure with early symptoms of HIV infection.
  • An inaccurate negative NAT result is possible since there is a small group of people who naturally decrease the amount of virus in their blood over time.
  • Small number of people, which can lead to an
  • The accuracy of NAT is reduced by taking pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP). An antibody or combination test at the same time is advised,  in order to help the doctor interpret the negative result of NAT. 6

Once a patient is diagnosed as HIV patient, the stage of the disease can be determined using several types of tests such as:

  1. CD4 count

 This test is used to detect the number of the CD4 cells present where a number lower than 200 cells/mm3   indicates that an HIV infection has progressed to AIDS. Since HIV targets and destroys this type of white blood cells, even if no symptoms are present.

 

  1.  Viral load

 This test measures the amount of virus in the blood.

 

  1.  Drug resistance

A resistance to certain anti-HIV medications by the strain of HIV can be specified using this blood test.

Other infections or complications can be detected using lab tests requested by the doctor, including:

  • Tuberculosis.
  • Hepatitis.
  • Toxoplasmosis.
  • Sexually transmitted infections.
  • Liver or kidney damage.
  • Urinary tract infection.
Treatment

No specific drug can completely cure HIV. However, using a combination of different types of drugs; antiretroviral therapy (ART (to control the virus, manage the symptoms, and decrease the progression rate is helpful. The best method is to choose a combination of at least three drugs from two classes, since the mechanism of how an anti-HIV drugs blocks the virus in each class varies. to avoid creating strains of HIV that are immune to single drugs.

The classes of anti-HIV drugs include:

  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

  These inhibitors block a protein needed by HIV to duplicate and include efavirenz, etravirine and nevirapine.

 

  • Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs)

NRTIs are defective versions of building blocks required for the duplication of HIV, including abacavir, and the combination drugs emtricitabine-tenofovir, and lamivudine-zidovudine.

 

  • Protease inhibitors (PIs)

 Protease; another protein that is needed for HIV duplication is blocked by PIs, including atazanavir, darunavir, fosamprenavir and indinavir.

  • CCR5 antagonists (CCR5s) (also called entry inhibitors)

 The CCR5 coreceptor located on the surface of certain immune cells, such as CD4 cells is blocked by this inhibitor, which does not allow HIV to enter the cell.

  • Fusion inhibitors

 This type of inhibitors stops the   blending of the HIV envelope with the host CD4 cell membrane, which disables the entrance of HIV into the CD4 cell. Such inhibitors include enfuvirtide and maraviroc.

 

  • Integrase inhibitors

. Integrase; a protein used by HIV for the insertion of its genetic material into CD4 cells, in this case is disabled. Examples of such inhibitors are raltegravir, elvitegravir and dolutegravir.  

Complications

Multiple complications accompany an HIV infection, such as:

  1. Opportunistic infections

The immune system is weakened by an HIV infection, which makes the body vulnerable and highly susceptible to numerous infections including:

  • Tuberculosis (TB)

It is with the most prevalence among opportunistic infections associated with HIV and in resource-poor nations it is considered a leading cause of death among patients with AIDS. .

 

  • Cytomegalovirus

 It is a herpes virus that can be transferred through the body fluids such as saliva, blood, urine, semen and breast milk. A normal healthy immune system causes the inactivation of this virus where it remains in its dormant phase inside the body. When the immune system is weakened by HIV, the virus resurfaces to cause possible damage the eyes, digestive tract, lungs and other organs. 

 

  • Candidiasis

It is considered a common HIV-related infection that causes inflammation accompanied by a thick white coating on the mucous membranes of the mouth, tongue, esophagus or vagina in a patient.

 

  • Cryptococcal meningitis

A fungus found in soil causes this common central nervous system infection that is associated with HIV.

 

  • Toxoplasmosis

 Toxoplasma Gondi parasite causes this type of fatal infection, where cats mainly spread this parasite. The parasite passes through the stool to a possibility of spreading to other animals and humans.

 

  • Cryptosporidiosis

 Taking in contaminated food or water is how this intestinal parasite that is found in animals spreads to cause an infection. The growth of this parasite in the intestines and bile ducts of a patient with AIDS leads to severe, chronic diarrhea. 8, 9

Other opportunistic infections include:

  • Bacillary angiomatosis.
  • Cryptosporidium enterocolitis (or other protozoal infections).
  • Mycobacterium avium complex (MAC) infection.
  • Pneumocystis jiroveci pneumonia.
  • Salmonella infection in the bloodstream.
  • Viral infection of the brain. 9

 

  1. Cancers

A body with a weakened immune system due to an HIV infection renders the body highly susceptible to numerous cancers including:

 

  • Kaposi's sarcoma

 It is a tumor that occurs in the blood vessels walls, in addition to the internal organs, including the digestive tract and lungs. Lesions on the skin and mouth, that are colored pink, red or purple in people with lighter skin or dark brown or black in people with darker skin begin to appear. The occurrence of this type of cancer is rare in normal people but is common in patients with HIV.

 

  • Lymphomas

The origin for this type of cancer is white blood cells that are present in lymph nodes, causing painless swelling of the lymph nodes in the neck, armpit or groin as an early sign.8

 

  1. Neurological complications

There is no direct infection to the nerve cells by HIV. However, various conditions that affect the nervous system may come out as result:

 

  • Dementia

 HIV-associated dementia or AIDS dementia could occur in advanced stages of HIV. Cognitive functions such as problems in thinking, understanding, and remembering are noticed and in dementia cognitive functions are damaged. This type of dementia can be life-threatening but can be usually prevented by taking antiretroviral medicines correctly.

 

 

  • Vacuolar myelopathy

Tiny holes start to develop in the fibers of the nerves of the spinal cord which leads to walking difficulties, particularly as the condition gets worse. Patients with AIDS that do not take medication or children with HIV are most commonly affected by this condition.

 

  • Psychological conditions

 Anxiety disorders, depression, hallucinations, and significant changes in behavior can often develop in patients with HIV or AIDS.

 

 

  • Neurosyphilis

Without treatment, syphilisincreases the progression and damaging of the nervous system. It can lead to loss of vision and hearing, dementia, and walking difficulties. 10

 

  1. Wasting syndrome

 This syndrome happens when a loss of at least 10% of body weight is observed, that is often associated with diarrhea, chronic weakness and fever. Aggressive treatment regimens are successful in reducing the number of cases of wasting syndrome but still many patients with AIDS are affected. 8

 

  1. Kidney disease

 The tiny filters of the kidney responsible for removing excess fluid and wastes from the bloodstream and passes them to the urine, is where the HIV-associated nephropathy (HIVAN) inflammation occurs.

Prevention

Prevention includes involving some practices that stop the spread of HIV such as:

  1. In sexual relation that transmit an  HIV infection , the risk is reduced by following some practices including:

 

  •  For every sexual intercourse, anew condom should be used, especially in the following cases:
  • If the partner’s HIV status is unknown.
  • People who use injected drugs.
  • People who have multiple partners.

Using water-based lubricants is more effective than using oil-based lubricants since they give more protection due to the fact of condoms are weakened by oil-based lubricants causing them to break.

  • Using combination drug emtricitabine-tenofovir can lower the risk of infection for individuals who are in high risk of sexually transmitted HIV infection.
  • Safe sex can be done using condoms which lowers the risk of infection, but preventing sexual transmission of the HIV can only be done by abstinence from having sex with an infected partner.

 

  1. Sharing and using unsterile needles, in addition to using secondhand needles or syringes should be avoided.

 

  1. Blood, plasma, body organs, or sperm from a donor should be checked for HIV before being administered. When there is a positive result for AIDS or positive HIV antibody tests, donation part must not be accepted.

 

  1. Elimination of mother-to-child transmission of HIV via providing ART drugs for both mother and child throughout the stages, where the infection could occur, since the spread of the infection can be during pregnancy, delivery or breastfeeding.

 

 

  1. Medical male circumcision can help in reducing the risk of having HIV.

 

Prognosis

HIV is a chronic condition that is incurable.  Prevention of complications and delaying progression to AIDS can be done achieved through following a treatment schedule.  Without treatment, the patient’s case will develop to AIDS. Long-term non progresses are the patients who develop AIDS very slowly, or never at all.

Prognosis depends on the stage:

  1. Acute HIV infection stage

 After 2-4 weeks of being infected with HIV, some patients but not all develop flu-like symptoms.

 

2. Clinical latency infection stage

When ART is provided, clinical latency can extend for several decades and without ART it only lasts for an average of 10 years with the exception of some patients who may progress through this stage faster.

 

  1. AIDS stage

 A life-expectancy of about three years is the prognosis for a patient that has reached this stage without being treated and has progressed into AIDS.  The prognosis is decreased to one year when the patient has a dangerous opportunistic illness and is left without treatment. If ART is being taken by the patient and is able to maintain a low viral load, then a near normal life span is expected and most probably will never progress to AIDS.

Epidemiology

HIV is considered as a major global public health issue. According to the World Health Organization (WHO) globally in 2015, these facts are stated:

  • The total number of people infected with HIV ranges from 34.0 to 39.8 million.
  • New cases of individuals infected with HIV ranges from 1.8 to 2.4 million.
  • From 940 000 to 1.3 million people have died because of HIV-related causes.
  • Two-thirds of the total of new HIV infections are recorded in the sub-Saharan Africa. It is considered as the most affected region, with 23.1 to 28.5 million people who have been infected with HIV.

 

It is estimated that only 60% of people with HIV know their status for the time being. The remaining 40% or over 14 million people still are in need to access HIV testing services to check their current status.

Globally, in the 2016, 16.1 to 19.0 million patients infected with HIV were receiving antiretroviral therapy (ART).

National HIV programs supported by the civil society and a range of development partners were successful between the years 2000 and 2015 in:

  • Decreasing the number of new HIV infections by 35%.
  • Decreasing the number AIDS-related deaths by 28%.

 

By the year 2030, 21 million can survive death and 28 million new cases can be prevented by providing ART to all patients infected with HIV and expanding prevention choices.